An Operant Intra-/Extra-dimensional Set-shift Task for Mice

Scheggia, Diego; Papaleo, Francesco

doi:10.3791/53503

Cited by 8 publications

(4 citation statements)

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“…A plexiglass barrier divided the two sides of the chamber and was slid up from below via an automated motor assembly. Behavioral procedures followed those of the "Extradimensional shift" protocol of Scheggia and Papaleo (2016) but without textural cues, and further details can be found there and in Scheggia et al (2014).…”

Section: Surgerymentioning

confidence: 99%

Rhythmic oscillations in the midbrain dopaminergic nuclei in mice

Oberto

Matsumoto

Pompili

et al. 2023

Front. Cell. Neurosci.

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IntroductionDopamine release in the forebrain by midbrain ventral tegmental nucleus (VTA) and substantia nigra pars compacta (SNc) neurons is implicated in reward processing, goal-directed learning, and decision-making. Rhythmic oscillations of neural excitability underlie coordination of network processing, and have been reported in these dopaminergic nuclei at several frequency bands. This paper provides a comparative characterization of several frequencies of oscillations of local field potential and single unit activity, highlighting some behavioral correlates.MethodsWe recorded from optogenetically identified dopaminergic sites in four mice training in operant olfactory and visual discrimination tasks.ResultsRayleigh and Pairwise Phase Consistency (PPC) analyses revealed some VTA/SNc neurons phase-locked to each frequency range, with fast spiking interneurons (FSIs) prevalent at 1–2.5 Hz (slow) and 4 Hz bands, and dopaminergic neurons predominant in the theta band. More FSIs than dopaminergic neurons were phase-locked in the slow and 4 Hz bands during many task events. The highest incidence of phase-locking in neurons was in the slow and 4 Hz bands, and occurred during the delay between the operant choice and trial outcome (reward or punishment) signals.DiscussionThese data provide a basis for further examination of rhythmic coordination of activity of dopaminergic nuclei with other brain structures, and its impact for adaptive behavior.

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Section: Surgerymentioning

confidence: 99%

Rhythmic oscillations in the midbrain dopaminergic nuclei in mice

Oberto

Matsumoto

Pompili

et al. 2023

Front. Cell. Neurosci.

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“…Patients with schizophrenia often have poor set-shifting capabilities, which translates to poor executive functioning [ 221 - 223 ]. This symptom is generally called executive inflexibility or a diminished ability to shift focus [ 223 , 224 ]. In ASST, a cognitive set is formed by creating a reinforced rule in a subject.…”

Section: Behavioral Tasks Measuring Cognitive Symptoms Of Schizophreniamentioning

confidence: 99%

Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update

Ang

Lee

Kim

et al. 2021

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Background: Schizophrenia is a serious mental illness that affects more than 21 million people worldwide. Both genetics and the environment play a role in its etiology and pathogenesis. Symptoms of schizophrenia are mainly categorized into positive, negative, and cognitive. One major approach to identify and understand these diverse symptoms in humans has been to study behavioral phenotypes in a range of animal models of schizophrenia. Objective: We aimed to provide a comprehensive review of the behavioral tasks commonly used for measuring schizophrenia-like behaviors in rodents together with an update of the recent study findings. Methods: Articles describing phenotypes of schizophrenia-like behaviors in various animal models were collected through a literature search in Google Scholar, PubMed, Web of Science, and Scopus, with a focus on advances over the last 10 years. Results: Numerous studies have used a range of animal models and behavioral paradigms of schizophrenia to develop antipsychotic drugs for improved therapeutics. In establishing animal models of schizophrenia, the candidate models were evaluated for schizophrenia-like behaviors using several behavioral tasks for positive, negative, and cognitive symptoms designed to verify human symptoms of schizophrenia. Such validated animal models were provided as rapid preclinical avenues for drug testing and mechanistic studies. Conclusion: Based on the most recent advances in the field, it is apparent that a myriad of behavior tests are needed to confirm and evaluate the congruency of animal models with the numerous behaviors and clinical signs exhibited by patients with schizophrenia

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“…These tasks are typically referred to as measures of behavioural flexibility, and so, I will refer to these tasks as such. Behavioural flexibility has received considerable interest in recent years (see, Figure 1.2) and procedures have been developed for use with primates (Groman et al, 2012;Kamigaki et al, 2011;Millan et al, 2010;Moore et al, 2005;Rygula et al, 2010;Zeamer et al, 2011), canines (Boutet et al, 2005;Brucks et al, 2019;Chan et al, 2002), felines (Irle & Markowitsch, 1984;Sherman et al, 2013), marsupials (Bonney & Wynne, 2002, 2004Masterton et al, 1974), alpaca (Abramson et al, 2018), sheep (Morton & Avanzo, 2011), pigs (Bolhuis et al, 2004), rodents (Boulougouris et al, 2007;Boulougouris & Tsaltas, 2008;Butts et al, 2013;Delatour & Gisquet-Verrier, 2000;Floresco et al, 2008;Nikiforuk & Popik, 2014;Ragozzino, Detrick, et al, 1999;Scheggia & Papaleo, 2016), lizards (Gaalema, 2011;Leal & Powell, 2012), birds (Gonzalez et al, 1967;MacDonald & Roberts, 2018), fish (Kuroda et al, 2017;Miletto Petrazzini et al, 2017;Parker et al, 2012), and invertebrates (Morrow & Smithson, 1969). Regardless of the specific paradigm used, they all measure how well behaviour adapts in response to changing reward contingencies.…”

Section: Measuring Cognitive Flexibility In Non-human Subjectsmentioning

confidence: 99%

The Effects of Repeated Dopamine D2 Receptor Antagonism on D2 Receptor Expression and Behavioural Inflexibility

Highgate¹

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Background: Reversal learning has been shown to improve as a function of dopamine D2 receptor expression, and manipulations that downregulated D2 expression also impaired behavioural flexibility. The possibility remains that an upregulation may facilitate reversal learning. Further, D2 receptor expression and reversal learning were compromised following repeated methamphetamine exposure. It stands to reason that restoration of receptor expression following methamphetamine exposure might prevent this impairment from occurring. Objectives: Develop a procedure for measuring reversal learning and determine whether repeated D2 receptor antagonism increases D2 receptor expression and improves behavioural flexibility in rats. Further, the possibility that this treatment would ameliorate behavioural inflexibility produced by prior methamphetamine exposure was examined. Methods: A task was developed to measure reversal learning. I systematically replicated an existing procedure, but then developed a novel procedure that focused on identifying a reasonable criterion for visual discrimination. To do this, male Sprague Dawley rats completed 25 days of visual discrimination. Various criteria requiring different levels of accuracy and persistence were retrospectively applied to the data and a single criterion was selected from these. The procedure was then extended to include three reversal tasks. In the next study, male Sprague-Dawley rats received repeated daily pretreatment with the dopamine D2 antagonist, eticlopride (0.0 or 0.3 mg/kg/day, IP, 14 days). Three days after treatment, whole-brain (minus olfactory bulbs and cerebellum) dopamine D2 receptor expression was measured using flow cytometry. Another cohort was exposed to the same regimen between the second and third reversal task to determine whether this treatment improved reversal learning. The final study was then conducted, the only difference from the previous study being that methamphetamine (0.0mg/kg or 2.0mg/kg, SC, 4 injections, 2 hours apart) was administered the day before eticlopride treatment commenced in order to produce behavioural inflexibility. Results: The criterion developed for the acquisition of visual discrimination was adopted for several reasons. First, the entire sample was able to meet the criterion. Second, the number of days to acquisition was equivalent irrespective of which visual cue served as the discriminative stimulus. Finally, accuracy was persistent both within and between test sessions. Importantly, therefore, these criteria eliminated confounds that might otherwise have been expected to impact reversal learning performance. The adjunct reversal tasks were typically completed within 2-5 test days, which was important since neuroadaptations can revert over time, and individual differences in performance were consistent across tasks. As expected, eticlopride treatment increased D2 receptor expression and improved reversal learning. Further, this improvement was predicted by baseline behavioural flexibility measures, such that, the improvement produced by repeated eticlopride treatment preferentially mpacted rats that were less behaviourally flexible prior to treatment. Methamphetamine treatment impaired reversal learning, but this impairment was prevented by repeated eticlopride treatment. Conclusions: Choice of criterion impacts behavioural performance in visual discrimination learning. D2 receptor expression is also a critical determinant of behavioural flexibility, irrespective of whether the discriminative stimulus is visual or spatial. Further, pre-existing, or experimentally produced behavioural inflexibility is sensitive to a treatment that upregulated D2 expression. Collectively, these findings support the critical role of D2 expression in reversal learning and suggest it is an effective target for facilitating behavioural flexibility.

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An Operant Intra-/Extra-dimensional Set-shift Task for Mice

Cited by 8 publications

References 23 publications

Rhythmic oscillations in the midbrain dopaminergic nuclei in mice

Rhythmic oscillations in the midbrain dopaminergic nuclei in mice

Behavioral Tasks Evaluating Schizophrenia-like Symptoms in Animal Models: A Recent Update

The Effects of Repeated Dopamine D2 Receptor Antagonism on D2 Receptor Expression and Behavioural Inflexibility

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